UNASSIGNED: Open surgery is gradually replaced by minimally invasive surgery, but few studies have reported the feasibility of laparoscopic pancreaticoduodenectomy (LPD) combined with vascular resection and reconstruction. The present study compared the efficacy of LPD with open pancreaticoduodenectomy (OPD) combined with portal vein/superior mesenteric vein (PV/SMV) resection and reconstruction for pancreatic cancer.
UNASSIGNED: The clinical data of patients who underwent PD combined with PV/SMV resection and reconstruction from March 2016 to August 2022 at our institution were retrospectively analyzed. The perioperative outcomes and survival outcomes were compared after propensity score matching (PSM).
UNASSIGNED: The original cohort included 64 patients. Sixteen pairs of patients were obtained by 1:1 PSM. The intraoperative blood loss was greater in the OPD group than in the LPD group (550 vs. 200 mL, P=0.04), and the PV clamp time was longer in the LPD group than in the OPD group (29.4 vs. 18.8 min, P<0.001). There was no significant difference in the incidence of postoperative complications. The median overall survival and progression-free survival were comparable between the two groups (P>0.05).
UNASSIGNED: LPD combined with PV/SMV resection and reconstruction is safe and feasible in selected patients and results in similar perioperative outcomes and prognosis as open surgery.

UNASSIGNED: Pancreatic cancer is the fourth most common cause of cancer-related death in the United States. Despite advancements in surgery and chemoradiation therapies, pancreatic cancer has a 5-year survival rate of only 11% in the United States. Cryoablation is emerging as a new and effective therapy for locally advanced pancreatic cancer and symptom palliation in metastatic disease. To our knowledge, the occurrence of disseminated intravascular coagulation (DIC) after cryoablation is rare.
UNASSIGNED: A 47-year-old woman with no significant past medical history was diagnosed with pancreatic cancer and underwent a Whipple procedure followed by chemotherapy with gemcitabine and paclitaxel. Due to the abdominal lymph nodes, peritoneum, right femur, and surrounding soft tissue metastases, she received systemic palliative chemotherapy with gemcitabine and paclitaxel and underwent right femur tumor excision, open reduction, and internal fixation, followed by radiation therapy. She continued to have persistent pain and underwent palliative percutaneous cryoablation of the metastatic tumor under computed tomography (CT) and ultrasound guidance. Immediately post procedure, she developed slow but continuous blood oozing at the ablation site, which was difficult to control despite compression dressings, reinforcement sutures, and local thrombin powder. The patient was transferred to the intensive care unit where she was noted to be hypotensive and tachycardic, with petechiae in both lower extremities. Laboratory studies were consistent with DIC and peripheral blood smear revealed multiple schistocytes. CT angiogram of the right lower extremity did not show any bleeding vessel amenable to embolization. She was transfused red blood cells, platelets, fresh frozen plasma, and cryoprecipitate. Despite multiple daily transfusions, she continued to have pain and remained persistently thrombocytopenic and coagulopathic. After discussion with the patient and her family, she chose to transition to comfort care measures and died.
UNASSIGNED: DIC is an unusual but life-threatening complication of advanced pancreatic cancer.

UNASSIGNED: With improving survival after pancreatic cancer (PC) resection, questions emerge concerning risk and patterns of metachronous tumors. We aimed to determine the incidence of multiple primary cancers among postoperative PC survivors.
UNASSIGNED: Patients undergoing PC surgery from 1975 to 2020 were identified in the Surveillance, Epidemiology, and End Results (SEER) registry. Standardized incidence ratios (SIRs) compared observed-to-expected cancers based on U.S. population rates. Cumulative incidence of secondary tumors was analyzed with Cox regression and cancer-specific survival with Kaplan-Meier curves.
UNASSIGNED: Of 6,100 resected PC patients, 267 (4.38%) developed multiple cancers over 6.2 years median follow-up period. Subsequent malignancies showed a rising cumulative incidence extending beyond 5 years. Lung cancer was the predominant second primary in both males (n=36, SIR 1.87) and females (n=32, SIR 2.17). Prostate (n=33) and breast (n=25) cancers were also common. Risk varied by latency period and gender.
UNASSIGNED: Postoperative PC patients face a measurable risk for secondary cancers. Enhanced long-term surveillance has the potential to improve early detection and outcomes in this survivor population. Our data provides real-world evidence which could help inform surveillance guidelines in the future.

UNASSIGNED: Pancreatic cancer (PC) is a lethal disease, especially metastatic PC. And it can be divided into two types: head pancreatic cancer (H-PC) and body and tail pancreatic cancer (BT-PC). Prior studies have proved that they have different overall survival (OS) and should be regarded as two different categories of PC. At present, there remains a gap in the field regarding OS across different primary tumor locations and metastatic sites, as well as the metastatic patterns associated with various primary tumor locations in patients with metastatic PC. Thus, our study aims to address this gap by analyzing data from a large population sourced from the Surveillance, Epidemiology, and End Results (SEER) database. The different prognosis of different primary tumor locations and metastatic sites may indicate that different primary locations and metastatic sites may require different therapy and follow-up strategy. It is hoped that these findings will lay the groundwork for future guideline updates and related research.
UNASSIGNED: Patients with pathologically confirmed stage IV metastatic PC from the National Cancer Institute\'s SEER program between 2010 and 2015 were included, excluding patients with various tumors, without specifying age, specific sites of metastasis, or OS. Data including age, race, gender, tumor size, T stage, N stage, grade, sites, number of metastatic sites, surgery, radiotherapy, chemotherapy and years of diagnoses were collected from the SEER database. OS was defined as the period from initial diagnosis to the date of death. Specific metastatic sites for the different primary locations of tumor were compared. Survival was analyzed by Cox regression analyses.
UNASSIGNED: Overall, 14,406 patients with metastatic PC were included in this research (7,104 of H-PC and 7,302 of BT-PC). Gender proportion, tumor size, T stage, N stage, number of metastatic sites surgery of the primary lesions and radiotherapy were different between BT-PC and H-PC. The proportion of only 1 metastatic site was 68.3% in H-PC compared with 58.3% in the BT-PC. The BT-PC was an independent risk factor for liver metastases compared with the H-PC [odds ratio (OR) =1.510; 95% confidence interval (CI): 1.320-1.727]. No matter for those with multiple metastases, or for those with solitary liver or lung metastases, patients with metastatic H-PC showed better OS (P<0.001, P=0.001, P=0.04, respectively). In patients with solitary liver metastases, worse OS was observed in the BT-PC than the H-PC [hazard ratio (HR) =1.109; 95% CI: 1.046-1.175].
UNASSIGNED: The metastatic BT-PC had worse OS and increased risk to suffer from liver and multiple metastases. Moreover, in patients with solitary metastases, those with liver metastases presented poorest survival.

Pancreatic cancer (PC) is a lethal disease that presents a considerable challenge to healthcare providers and patients, given its low survival rate. However, recent advancements in precision medicine and innovative technologies have transformed the management of this disease. Among these advancements, extracellular vesicles (EVs) have emerged as crucial players in cancer progression. In PC, EVs play a pivotal role by facilitating cell-cell communication, impeding immune response, promoting cancer cell proliferation and survival, and supporting angiogenesis and chemoresistance. Cancer-derived EVs have a distinct oncogenic composition supporting tumour development and progression. Hence, they are critical biomarker candidates for various cancers, including PC. Notably, EVs can be isolated from diverse biological fluids such as blood, urine, and saliva, making them an ideal minimally invasive diagnostic and monitoring tool for PC patients. Despite the promising findings in the field of EVs, clinical validation as biomarkers is lacking. Furthermore, EVs being biocompatible, can act as drug carriers, delivering therapeutic molecules directly to cancer cells while minimizing toxicity to healthy cells. Therefore, understanding the role of EVs as biomarkers and their potential as drug cargo vehicles may revolutionise early detection, prognostication, and treatment in cancer. This mini-review summarises the latest understanding of their role in intercellular communication, involvement as potential biomarkers and drug carriers.

UNASSIGNED: Pancreatic cancer (PC) is an aggressive disease with a very poor prognosis. The insidious onset, rapid progression, and resistance to conventional therapies mark the imperious need for novel biomarkers and therapeutic targets. The pituitary tumor transforming gene 1 (PTTG1), implicated in tumorigenesis and cellular transformation, has been studied in various cancers, however, its role and mechanisms in PC remain to be elucidated for better understanding the disease pathology and in enhancing patient management strategies.
UNASSIGNED: The present study examined the PTTG1 messenger RNA (mRNA) expression levels and clinical significance through meta-analysis based on The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Immunohistochemistry (IHC) was used to measure PTTG1 protein levels in PC and adjacent non-cancerous tissues. A correlation was observed between PTTG1 expression and some clinical characteristics based on the TCGA and IHC data. Univariate and multivariate Cox regressions were used to identify independent prognostic factors. Kaplan-Meier (KM) survival analysis was performed. The co-expressed genes of PTTG1 were determined by integrating online tools, and the enrichment analyses were performed to determine PTTG1-related pathways and hub co-expressed genes.
UNASSIGNED: PTTG1 was highly expressed in PC tissues based on the TCGA, GEO, and IHC data. The combined standard mean difference (SMD) values of PTTG1 expression based on TCGA and GEO databases was 1.02 [95% confidence interval (CI): 0.74-1.30]. The area under the curve (AUC) based on the summary receiver operating characteristic (sROC) curve was 0.93 (95% CI: 0.90-0.95). PTTG1 overexpression was remarkably correlated with an inferior overall survival (OS). A total of 367 genes were identified as co-expressed genes of PTTG1 in PC and were mainly involved in the cell cycle pathway. The four identified core genes were CDK1, CCNA2, CDC20, and MAD2L1.
UNASSIGNED: The upregulated expression of PTTG1 plays an essential role in PC\'s progression as a biomarker.

The advent of high throughput DNA sequencing is providing massive amounts of tumor-associated mutation data. Implicit in these analyses is the assumption that, by acquiring a series of hallmark changes, normal cells evolve along a neoplastic path. However, the lack of correlation between cancer risk and global exposure to mutagenic factors provides arguments against this model. This suggested that additional, non-mutagenic factors are at work in cancer development. A candidate determinant is TROP2, that stands out for its expression in the majority of solid tumors in human, for its impact on the prognosis of most solid cancers and for its role as driver of cancer growth and metastatic diffusion, through overexpression as a wild-type form. The Trop-2 signaling network encompasses CREB1, Jun, NF-κB, Rb, STAT1 and STAT3, through induction of cyclin D1 and MAPK/ERK. Notably, Trop-2-driven pathways vastly overlap with those activated by most functionally relevant/most frequently mutated RAS and TP53, and are co-expressed in a large fraction of individual tumor cases, suggesting functional overlap. Mutated Ras was shown to synergize with the TROP2-CYCLIND1 mRNA chimera in transforming primary cells into tumorigenic ones. Genomic loss of TROP2 was found to promote carcinogenesis in squamous cell carcinomas through modulation of Src and mutated Ras pathways. DNA methylation and TP53 status were shown to cause genome instability and TROP gene amplification, together with Trop-2 protein overexpression. These findings suggest that mutagenic and the TROP2 non-mutagenic pathways deeply intertwine in driving transformed cell growth and malignant progression of solid cancers.

The shift in glucose utilization from oxidative phosphorylation to glycolysis is the hallmark of tumor cells. The overexpression of ENO1, one of the key enzymes in the glycolysis process, has been identified in several cancers, however, its role in pancreatic cancer (PC) is yet unclear. This study identifies ENO1 as an indispensable factor in the progression of PC. Interestingly, ENO1-knockout could inhibit cell invasion and migration and prevent cell proliferation in pancreatic ductal adenocarcinoma (PDAC) cells (PANC-1 and MIA PaCa-2); meanwhile, tumor cell glucose uptake and lactate excretion also decreased significantly. Furthermore, ENO1-knockout reduced colony formation and tumorigenesis in both in vitro and in vivo tests. In total, after ENO1 knockout, 727 differentially expressed genes (DEGs) were identified in PDAC cells by RNA-seq. Gene Ontology enrichment analysis revealed that these DEGs are mainly associated with components such as the \'extracellular matrix\' and \'endoplasmic reticulum lumen\', and participate in the regulation of signal receptor activity. Kyoto Encyclopedia of Genes and Genomes pathway analysis revealed that the identified DEGs are associated with pathways, such as \'fructose and mannose metabolism\', \'pentose phosphate pathway, and \'sugar metabolism for amino and nucleotide. Gene Set Enrichment Analysis showed that ENO1 knockout promoted the upregulation of oxidative phosphorylation and lipid metabolism pathways-related genes. Altogether, these results indicated that ENO1-knockout inhibited tumorigenesis by reducing cell glycolysis and activating other metabolic pathways by altering the expression of G6PD, ALDOC, UAP1, as well as other related metabolic genes. Concisely, ENO1, which plays a vital role in the abnormal glucose metabolism in PC, can be exploited as a target to control carcinogenesis by reducing aerobic glycolysis.

Accumulating evidence (mainly from experimental research) suggests that metformin possesses anticancer properties through the induction of apoptosis and inhibition of the growth and proliferation of cancer cells. However, its effect on the enzymes responsible for histone acetylation status, which plays a key role in carcinogenesis, remains unclear. Therefore, the aim of our study was to evaluate the impact of metformin on histone acetyltransferases (HATs) (i.e., p300/CBP-associated factor (PCAF), p300, and CBP) and on histone deacetylases (HDACs) (i.e., SIRT-1 in human pancreatic cancer (PC) cell lines, 1.2B4, and PANC-1). The cells were exposed to metformin, an HAT inhibitor (HATi), or a combination of an HATi with metformin for 24, 48, or 72 h. Cell viability was determined using an MTT assay, and the percentage of early apoptotic cells was determined with an Annexin V-Cy3 Apoptosis Detection Assay Kit. Caspase-9 activity was also assessed. SIRT-1, PCAF, p300, and CBP expression were determined at the mRNA and protein levels using RT-PCR and Western blotting methods, respectively. Our results reveal an increase in caspase-9 in response to the metformin, indicating that it induced the apoptotic death of both 1.2B4 and PANC-1 cells. The number of cells in early apoptosis and the activity of caspase-9 decreased when treated with an HATi alone or a combination of an HATi with metformin, as compared to metformin alone. Moreover, metformin, an HATi, and a combination of an HATi with metformin also modified the mRNA expression of SIRT-1, PCAF, CBP, and p300. However, metformin did not change the expression of the studied genes in 1.2B4 cells. The results of the Western blot analysis showed that metformin diminished the protein expression of PCAF in both the 1.2B4 and PANC-1 cells. Hence, it appears possible that PCAF may be involved in the metformin-mediated apoptosis of PC cells.

UNASSIGNED: Pancreatic cancer (PC) is one of the most malignant cancers of the gastrointestinal tract. However, the study of targeted therapy research in PC is not very thorough. Therefore, targeted molecular markers are needed to aid in the diagnosis and treatment of PC.
UNASSIGNED: In our research, we investigated the biological functions and molecular mechanism of microRNA-543 in PC. Western blotting (WB) and quantitative real-time polymerase chain reaction (qRT-PCR) were performed to analyze the transcription and protein expression of microRNA-543, Serine/threonine kinase 31 (STK31), and LINC00847 in BxPC-3 and PANC-1 cells. Subsequently, Cell Counting Kit-8 (CCK-8), Transwell, colony formation, and flow cytometry (FCM) assays were utilized to evaluate cell growth, migration, invasion, and apoptosis. WB and fluorescence in-situ hybridization (FISH) were used to evaluate the epithelial-mesenchymal transition (EMT) process and subcellular localization. RNA immunoprecipitation (RIP), double luciferase reporter, and RNA-pull down assays were performed to determine the targeting relationship between microRNA-543 and STK31 or microRNA-543 and LINC00847.
UNASSIGNED: While microRNA-543 expression was discovered to be low in PC, LINC00847 and STK31 were overexpressed at significant levels. MicroRNA-543 knockdown dramatically increased PC cell growth, invasion, metastasis, and EMT, as well as decreased apoptosis in functional studies. Furthermore, microRNA-543 and STK31 were found to be mutual targets. LINC00847 acted as a molecular sponge for microRNA-543 and a competitive endogenous RNA (ceRNA) for STK31, thereby increasing STK-31 transcription.
UNASSIGNED: Our results suggest that microRNA-543, through the LINC00847/microRNA-543/STK31 axis, plays a role in the development of PC as a tumor suppressor. As a result, microRNA-543 may prove to be an effective diagnostic and therapeutic target for PC.